Melanoma has recently emerged as a poster child for targeted therapies and immunotherapies, with game-changing BRAF and immune checkpoint inhibitors now in clinical trials and with approved clinical indications. One highly anticipated use of novel therapeutic agents is in the adjuvant setting. Adjuvant BRAF and/or immune checkpoint inhibition may positively affect the survival of melanoma patients diagnosed at earlier stages but still at high risk for postsurgical relapses. BRAF V600 mutations and, potentially, melanoma-associated immunity are predictive biomarkers for responses to these novel therapies. Emerging evidence points to these predictive biomarkers doubling as prognostic biomarkers for high-risk stage III patients, promising to help stratify these patients for the application of novel adjuvant therapies.